1. Field of the Invention
The present invention relates to a fusion of a technique in a biotechnology and a nanotechnology that realizes a highly integrated substrate device and, more specifically, to a technique for manufacturing a nanobio device in which a group of cells are arranged in array according to a rule which is formed by imitating a certain anatomy structure.
2. Description of the Related Art
In the field of biotechnology in recent years, individual cell can be controlled freely owing to improvement of laser trapping technique and the like, and a shape having dimensions or design according to an intended use can be processed on a substrate since high-integration degree or high-speed degree of the substrate device is enhanced due to recent development of nanotechnology. This technique has reached a level which intends to manufacturing of a nanobio device in which a group of cells are arranged in array according to a rule obtained by imitating a certain anatomy structure. In other words, organization of a cultured cell on a nanodevice in a high level which is substantially in vivo state, which has been believed to be difficult in the related art is in the course of realization owing to the fusion of these technologies. Consequently, it can be expected as an effective tool only in manufacture of material for regeneration medicine, but also in analysis of intercellular action which has been difficult to be figured out in vitro. On the other hand, exhaustive analysis such as transcriptome analysis using a DNA micro-array method or proteome using two-dimensional electrophoresis and a mass spectrograph is utilized in various fields of medical science and biology, and a high throughput analysis attracts attention. It is because not only understanding of the molecules in individual level, but also exhaustive understanding of diversification of molecular mechanism in a network of cells by the high-throughput analysis is required as the entire gene array retained by each living organism is made known by a genome project or a DNA project. Such tendency of new technology is in the course of developing an age of analysis not only by gene expression or an interaction of proteins, but also on a level of living cells by using a system of nanobio device combined with the high-throughput approach, and establishment of anew system as a successor of a biological test and application to a medicament screening and so on are now in the level of being promised.
Regeneration medicine is one of the fields of research which gets the highest attention recently. The prime reason is that it is expected as a medical practice in a new century which supplements serious lack of transplant internal organs. However, it is still in the level of cell transplant treatment at the present moment, and is not in the level of regenerating the internal organ itself. The reasons why regeneration of the internal organs is not realized are as follows. The internal organ has a regular, but very complicated structure such that the internal organ is composed of a plurality of cells, and that a vascular network for supplying nutrition and oxygen is present therein. Therefore, it has been considered that even though it is possible to provide individual cells, it is very difficult to build an internal organ itself therefrom. In other words, with the conventional technology, it is extremely difficult to arrange and constitute an organization of each internal organ by controlling the cells.
However, owing to innovation of laser manipulator technique and development of micro-fabrication technique in the field of nanotechnology in recent years, the cell itself is now able to enjoy benefits of nanotechnology sufficiently. Accordingly, although it is still far from the level at which the internal organ itself can be regenerated at the present moment, it is now possible to arrange cells as desired in a state of segments of an internal organ on an artificial substrate. Therefore, if the substrate having cells arranged thereon can be built using this technique, a three-dimensional internal organ structure can be manufactured by laminating the same into a plurality of layers. Furthermore, if the substrate can be built with a bio-compatible substance such as collagen or hyaluronic acid, an adverse reaction with respect to the cells can further be reduced, and hence manufacture of an internal organ unit that can be transplanted will also be possible in future in combination with a technique of revascularization.
As a source to be used actually for building an internal organ, a systematic stem cell such as a bone marrow cell or an embryonic-stem cell (ES cell) is considered as one of examples. Although the systematic stem cell has a problem such as cell fusion, there is an advantage such that immunological rejection may not occur in theory since it can be taken from an adult and since it is a cell of his/her own, which is one of factors fascinating for building an internal organ. On the other hand, in a problem regarding the embryonic-stem cell, a way to practical use in the field of medical practice is now being explored since a gene relating to formation of a teratoid tumor, which has been an obstacle for transplantation, is now identified and, as regards immunological rejection, a clone embryo technique for transplanting a somatic nucleus of a patient to a fertilized egg and establishing the embryonic-stem cell is enabled. Further development of research on such stem cells to enable foundation of a system in which these stem cells can be supplied as a source (individual cells) for building an internal organ is required for the internal organ regeneration by means of nanotechnology.
[Non Patent Document 1] Oode K, Furuya T, Harada K, Kawaguchi S, Yamamoto K, Hirano T. Sasaki K. “The development of a cell array and its combination with laser-scanning cytometry allows a high-throughput analysis of nuclear DNA content” Am J Pathol. 157(3) pp. 723-728 September 2000.
[Non Patent Document 2] Teratani Ko, Ochiai Takahiro, “Stem Cell, ES cell—Mesenchymal Stem Cell” Regeneration medicine Vol. 3, No. 4 pp. 126-133, 2004)